Head and Neck Cancers: Optimum Treatment Combination of Immunotherapy, Novel Agents with Standard Treatments in the Era of Personalized Medicine

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 May 2022)

Special Issue Editors


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Guest Editor
King's College London, University of Birmingham, Birmingham, UK
Interests: head and neck cancer; treatment; biomarker; liquid biopsy; breast cancer

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Guest Editor
1. Center for Oncological Research Antwerp, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium
2. Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium
Interests: cancer biology; cancer therapy; oncology; toxicity; pharmacodynamics; chemotherapy; treatment; cancer; tumors; pharmacokinetics
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Guest Editor
Head of Translational Radiobiology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Erlangen, Germany
Interests: immune modulation by radiation; tumor immunology; hyperthermia; vaccination; osteoimmunological mechanisms of low-dose radiation therapy; translational immune monitoring; combined radio- immunotherapies; prognostic and predictive immune biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and neck cancers are very heterogeneous, and the majority of these cancers are squamous cell carcinomas (HNSCCs) related to long-term smoking and alcohol intake. However, there has been an increasing incidence of oropharyngeal cancers due to human papillomavirus (HPV) infection. The HPV-induced oropharyngeal SCCs have a different biology to HPV-negative HNSCCs, and patients with these tumors respond better to chemoradiation and have a better prognosis. As a result, there have been several strategies to de-escalate treatments for these patients in order to reduce the long-term toxicities from chemoradiation. However, de-escalation using cetuximab replacing cisplatin chemotherapy have shown inferior survival outcomes without reducing acute and long-term toxicities. Therefore, it remains an open question how best to de-escalate treatment for these HPV oropharyngeal cancers. Could immunotherapy or other novel agents sensitize to radiotherapy to ensure equivalent or better outcomes than with chemoradiation in these patients? In addition, certain patients present with very aggressive tumors and the disease relapses or progresses soon after radiotherapy or chemoradiation, suggesting a benefit from treatment intensification. Could immunotherapy or novel agents be integrated as part of the standard treatments, and if so, how would be best to combine these treatments (concurrent versus sequential)? A fundamental understanding of how these tumors behave and respond to different treatments would be key to achieving optimum treatment combination with minimal toxicities.

An anti-PD1 checkpoint inhibitor is now approved as a first-line and second-line treatment in recurrent and metastatic HNSCC. Multiple ongoing trials are assessing the role of these agents in curative settings in combination with radiotherapy and/or chemotherapy. There remains an open question of how best to combine immunotherapy with the standard treatments and the sequence of their combination. In addition, multiple novel agents including targeted therapies and immunotherapy are being tested in clinical trials, and how these agents would eventually fit in with the treatment pathways in HNSCC remains to be elucidated. Lastly, biomarker-driven clinical studies based on genetic aberrations have shown great promise and raised hype, but the results have, to date, been disappointing. It is possible that an optimum treatment combination to prevent drug resistance and the incorporation of immunotherapy may improve the outcomes of patients treated with therapies targeted against specific genomic aberrations.

We are pleased to invite you to contribute to these Special Issues on the biology, rationale, and preclinical and clinical evidence on the optimum treatment combination of immunotherapy and novel agents with radiotherapy and/or chemotherapy to improve the treatment outcomes in head and neck cancers. We welcome high-quality review and original research articles covering basic, translational, and clinical studies related to these areas in head and neck cancers.

Dr. Anthony Kong
Dr. Jan B. Vermorken
Prof. Dr. Udo S. Gaipl
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Head and neck cancer
  • Oropharyngeal cancer
  • Chemotherapy
  • Immunotherapy
  • Biomarker
  • Targeted therapies
  • Checkpoint inhibitor

Published Papers (3 papers)

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Research

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11 pages, 1256 KiB  
Article
A Prospective Real-World Multi-Center Study to Evaluate Progression-Free and Overall Survival of Radiotherapy with Cetuximab and Platinum-Based Chemotherapy with Cetuximab in Locally Recurrent Head and Neck Cancer
by Markus Hecht, Dennis Hahn, Philipp Wolber, Matthias G. Hautmann, Dietmar Reichert, Steffi Weniger, Claus Belka, Tobias Bergmann, Thomas Göhler, Manfred Welslau, Christina Große-Thie, Orlando Guntinas-Lichius, Jens von der Grün, Panagiotis Balermpas, Katrin Orlowski, Diethelm Messinger, Karsten G. Stenzel and Rainer Fietkau
Cancers 2021, 13(14), 3413; https://doi.org/10.3390/cancers13143413 - 8 Jul 2021
Cited by 7 | Viewed by 2561
Abstract
Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy [...] Read more.
Treatment options of locoregional recurrent head and neck squamous cell cancer (HNSCC) include both local strategies as surgery or re-radiotherapy and systemic therapy. In this prospective, multi-center, non-interventional study, patients were treated either with platinum-based chemotherapy and cetuximab (CT + Cet) or re-radiotherapy and cetuximab (RT + Cet). In the current analysis, progression-free survival (PFS) and overall survival (OS) were compared in patients with locoregional recurrence. Four hundred seventy patients were registered in 97 German centers. After exclusion of patients with distant metastases, a cohort of 192 patients was analyzed (129 CT + Cet, 63 RT + Cet). Radiotherapy was delivered as re-irradiation to 70% of the patients. The mean radiation dose was 51.8 Gy, whereas a radiation dose of ≥60 Gy was delivered in 33% of the patients. Chemotherapy mainly consisted of cisplatin/5-flurouracil (40%) or carboplatin/5-flurouracil (29%). The median PFS was 9.2 months in the RT + Cet group versus 5.1 months in the CT + Cet group (hazard ratio for disease progression or death, 0.40, 95% CI, 0.27–0.57, p < 0.0001). Median OS was 12.8 months in the RT + Cet group versus 7.9 months in the CT + Cet group (hazard ratio for death, 0.50, 95% CI, 0.33–0.75, p = 0.0008). In conclusion, radiotherapy combined with cetuximab improved survival compared to chemotherapy combined with cetuximab in locally recurrent HNSCC. Full article
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Review

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13 pages, 1732 KiB  
Review
The Therapeutic Potential of Imidazole or Quinone-Based Compounds as Radiosensitisers in Combination with Radiotherapy for the Treatment of Head and Neck Squamous Cell Carcinoma
by Abul Azad and Anthony Kong
Cancers 2022, 14(19), 4694; https://doi.org/10.3390/cancers14194694 - 27 Sep 2022
Cited by 5 | Viewed by 1490
Abstract
The addition of platinum chemotherapy to primary radiotherapy (chemoradiation) improves survival outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but it carries a high incidence of acute and long-term treatment-related complications, resulting in a poor quality of life. In addition, [...] Read more.
The addition of platinum chemotherapy to primary radiotherapy (chemoradiation) improves survival outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but it carries a high incidence of acute and long-term treatment-related complications, resulting in a poor quality of life. In addition, patients with significant co-morbidities, or older patients, cannot tolerate or do not benefit from concurrent chemoradiation. These patients are often treated with radiotherapy alone resulting in poor locoregional control and worse survival outcomes. Thus, there is an urgent need to assess other less toxic treatment modalities, which could become an alternative to chemoradiation in HNSCC. Currently, there are several promising anti-cancer drugs available, but there has been very limited success so far in replacing concurrent chemoradiation due to their low efficacy or increased toxicities. However, there is new hope that a treatment strategy that incorporates agents that act as radiosensitisers to improve the efficacy of conventional radiotherapy could be an alternative to more toxic chemotherapeutic agents. Recently, imidazole-based or quinone-based anti-malarial compounds have drawn considerable attention as potential radiosensitisers in several cancers. Here, we will discuss the possibility of using these compounds as radiosensitisers, which could be assessed as safe and effective alternatives to chemotherapy, particularly for patients with HNSCC that are not suitable for concurrent chemotherapy due to their age or co-morbidities or in metastatic settings. In addition, these agents could also be tested to assess their efficacy in combination with immunotherapy in recurrent and metastatic settings or in combination with radiotherapy and immunotherapy in curative settings. Full article
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25 pages, 991 KiB  
Review
Vaccine-Based Immunotherapy for Head and Neck Cancers
by Simon Beyaert, Jean-Pascal Machiels and Sandra Schmitz
Cancers 2021, 13(23), 6041; https://doi.org/10.3390/cancers13236041 - 30 Nov 2021
Cited by 18 | Viewed by 3687
Abstract
In 2019, the FDA approved pembrolizumab, a monoclonal antibody targeting PD-1, for the first-line treatment of recurrent or metastatic head and neck cancers, despite only a limited number of patients benefiting from the treatment. Promising effects of therapeutic vaccination led the FDA to [...] Read more.
In 2019, the FDA approved pembrolizumab, a monoclonal antibody targeting PD-1, for the first-line treatment of recurrent or metastatic head and neck cancers, despite only a limited number of patients benefiting from the treatment. Promising effects of therapeutic vaccination led the FDA to approve the use of the first therapeutic vaccine in prostate cancer in 2010. Research in the field of therapeutic vaccination, including possible synergistic effects with anti-PD(L)1 treatments, is evolving each year, and many vaccines are in pre-clinical and clinical studies. The aim of this review article is to discuss vaccines as a new therapeutic strategy, particularly in the field of head and neck cancers. Different vaccination technologies are discussed, as well as the results of the first clinical trials in HPV-positive, HPV-negative, and EBV-induced head and neck cancers. Full article
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